A Therapeutic Nanovaccine that Generates Anti-amyloid Antibodies and Amyloid-specific Regulatory T cells for Alzheimer's Disease.

Alzheimer's disease (AD), the most common cause of dementia, is a complex condition characterized by multiple pathophysiological mechanisms including amyloid-β (Aβ) plaque accumulation and neuroinflammation in the brain. Current immunotherapy approaches, such as anti-Aβ monoclonal antibody (mAb) therapy, Aβ vaccines, and adoptive regulatory T (Treg) cell transfer target a single pathophysiological mechanism that may lead to unsatisfactory therapeutic efficacy. Furthermore, Aβ vaccines often induce T helper 1 (Th1) cell-mediated inflammatory responses. Here, we developed a nanovaccine composed of lipid nanoparticles loaded with Aβ peptides and rapamycin, which targets multiple pathophysiological mechanisms, exhibits the combined effects of anti-Aβ antibody therapy and adoptive Aβ-specific Treg cell transfer, and can overcome the limitations of current immunotherapy approaches for AD. Nanovaccines effectively deliver rapamycin and Aβ peptides to dendritic cells, produce both anti-Aβ antibodies and Aβ-specific Treg cells, remove Aβ plaques in the brain, alleviate neuroinflammation, prevent Th1 cell-mediated excessive immune responses, and inhibit cognitive impairment in mice. Nanovaccines show higher efficacy in cognitive recovery than an Aβ vaccine. Unlike anti-Aβ mAb therapy and adoptive Treg cell transfer, both of which require complicated and costly manufacturing processes, nanovaccines are easy-to-prepare and cost-effective. Nanovaccines could represent a novel treatment option for AD. This article is protected by copyright. All rights reserved.